HIDEA syndrome: A rare cause of congenital hypoventilation in a premature infant

Abstract

Background: HIDEA (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities) syndrome is a rare and novel disease. We describe a premature patient who required extensive work up for his hypoventilation with a diagnosis of HIDEA syndrome.Case Description: The patient was born to a pair of consanguineous parents at 32-week gestation. His intermittent bradypnoea requiring significant respiratory support during his postnatal clinical course was atypical for bronchopulmonary dysplasia and this required further extensive work up to look for a cause for his hypoventilation. A trio whole exon sequencing was done which identified homozygous variants in P4HTM, in keeping with the diagnosis of autosomal recessive HIDEA syndrome. He is currently doing well on BiPAP 18 cm H2O / 8 cm H2O, Rate 30 breaths per minute in room air and full nasogastric feeding. He also has cortical blindess and severe global developmental delay. Conclusion:Early diagnosis is crucial to optimise adequate ventilatory management including early tracheostomy as many require lifelong continuous or intermittent ventilation. This minimises the complications of chronic hypoxia and reduces mortality risk.

HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H‐TM protein

“…Here, we report six new unrelated patients and review the clinical details of all 24 previously published HIDEA patients. The phenotype of the patients identified in the current study is comparable to the phenotype described in the literature 1,2,5–8 . One patient in this study has dystonia, which has not previously been described in HIDEA.…”

“…To the authors' knowledge, P4HTM p.(Glu312Lys), p.(Thr361Ile), and p.(Trp457*) variants have not previously been reported as disease‐causing, hence expanding the genotypic spectrum of the disease. To date, including the cases reported in the present study, there are 15 different pathogenic variants of P4HTM reported to cause HIDEA syndrome 1,2,5–8 …”

“…The phenotype of the patients identified in the current study is comparable to the phenotype described in the literature. 1,2,[5][6][7][8] One patient in this study has dystonia, which has not previously been described in HIDEA. Dystonia is a movement disorder thought to result from an abnormality or damage to the basal ganglia or other brain regions controlling movement.…”

“…To date, including the cases reported in the present study, there are 15 different pathogenic variants of P4HTM reported to cause HIDEA syndrome. 1 , 2 , 5 , 6 , 7 , 8 …”

“…4 To the authors' knowledge, 24 HIDEA patients with 12 different disease-associated P4HTM variants have been described in the medical literature. 1,2,[5][6][7][8] Here, we review the clinical and molecular data from all the published patients and describe six previously unpublished patients with HIDEA caused by five different biallelic pathogenic P4HTM variants.…”